The pharmacologically active lipid amides N-acylphosphatidylethanolamine (NAPE) and N-acylethanolamine (NAE) reach high levels in the 24 hour infarcted canine myocardium. Because of their pharmacologic activities, their formation may be of critical importance to the ischemic and infarcting heart. The specific aims of this project are to (1) determine the time course of formation of NAPE and NAE in the ischemic and infarcting canine myocardium and determine the levels to which they accumulate. The coronary artery ligated dog will be used as amodel and lipid amide formation correlated to regional myocardial blood flow; (2) determine the effects of NAE on isolated heart sarcolemmal (SL) and sarcoplasmic reticulum (SR) function). The effects of chemically synthesized NAEs on isolated cardiac SL ouabain binding and Na+,K+-ATPase activity, and on SR Ca2+ pump activity will be assessed; (3) evaluate the effects of NAEs on the normal and ischemic heart. The isolated working heart will serve as a model in these studies. The overall long-range goal of this grant, therefore, is to critically evaluate the formation of lipid amides as being part of a naturally-occurring myocardial defense mechanism aimed at limiting the spread and degree of ischemic damage.